Transcriptomics

Dataset Information

0

The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus


ABSTRACT: We investigated the roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficient Irf-3-/-7-/- mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 hours after infection; however, they remained resistant to lethal infection. IFN-α/β was induced similarly in wild-type and Irf-3-/- mice post DENV infection, whereas in the Irf-7-/- and Irf-3-/-7-/- mice, significantly low levels of IFN-α/β expression was observed within 24 hours post-infection. IFN-stimulated gene (ISG) induction was also delayed in Irf-3-/-7-/- mice relative to wild-type and single-deficient mice. In particular, Cxcl10 and Ifnα2 were rapidly induced independently of both IRF-3 and IRF-7 in the Irf-3-/-7-/- mice with DENV infection. Higher levels of serum IFN-γ, IL-6, CXCL10, IL-8, IL-12 p70, and TNF were also observed in Irf-3-/-7-/- mice 24 hours after infection, at which time point viral titers peaked and started to be cleared. Antibody-mediated blockade experiments revealed that IFN-γ, CXCL10, and CXCR3 function to restrict DENV replication in Irf-3-/-7-/- mice. Additionally, the ISGs Cxcl10, Ifit1, Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that does not involve IFN-γ signaling for protection against DENV. Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-α/β response; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti-DENV immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE49871 | GEO | 2013/08/15

SECONDARY ACCESSION(S): PRJNA215223

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2013-08-15 | E-GEOD-49871 | biostudies-arrayexpress
2017-11-07 | GSE104189 | GEO
2023-11-08 | GSE199821 | GEO
2008-06-14 | E-GEOD-6092 | biostudies-arrayexpress
2020-01-13 | GSE132367 | GEO
2007-01-05 | GSE6092 | GEO
2010-08-22 | GSE21018 | GEO
2016-06-01 | GSE70429 | GEO
2019-07-04 | GSE128211 | GEO
2016-06-01 | E-GEOD-70429 | biostudies-arrayexpress